Toxoplasma gondii peptide ligands open the gate of the HLA class I binding groove

摘要

HLA class I presentation of pathogen-derived peptide ligands is essential for CD8+ T cell recognition of infected cells. Currently, little data exist pertaining to peptides that are presented after infection. Herein we purify HLA-A*02:01 complexes from infected cells and characterize the peptide ligands using LCMS. We identify 195 encoded ligands originating from both secreted and cytoplasmic proteins. Surprisingly, ligands are significantly longer than uninfected host ligands, and these longer pathogen derived peptides maintain a canonical N-terminal binding core yet exhibit a C-terminal extension of 1-30 amino acids. Structural analysis demonstrates that binding of extended peptides opens the HLA class I F' pocket, allowing the C-terminal extension to protrude through one end of the binding groove. In summary, we demonstrate that unrealized structural flexibility makes MHC class I receptive to parasite-derived ligands that exhibit unique C-terminal peptide extensions.